Phase-change and shape-change materials

ABSTRACT

Apparatus and methods are described for killing cancer cells ( 44 ) of a subject, the subject having cancer cells and healthy cells. The apparatus includes a plurality of first molecules ( 40 ) configured to be coupled to the cancer cells to a greater extent than to the healthy cells, in response to being administered to the subject. A plurality of clusters ( 42 ) of phase-change molecules are provided, each of the clusters coupled to a respective one of the first molecules. An energy transmission unit ( 50 ) kills cancer cells coupled to the first molecules by heating the cancer cells, by transmitting energy toward the clusters that selectively heats the clusters. Other embodiments are also described.

CROSS REFERENCES TO RELATED APPLICATIONS

The present application is a U.S. national phase of PCT Application no.PCT/IL2010/000683 to Hof, filed Aug. 22, 2010, which claims priorityfrom: U.S. Application Nos. 61/275,068; 61/275,071 and 61/275/089, eachfiled on Aug. 24, 2009, the contents of which are all incorporatedherein by reference.

FIELD OF EMBODIMENTS OF THE INVENTION

Some applications of the present invention generally relate to implantedmedical apparatus. Specifically, some applications of the presentinvention relate to the use of phase-change and shape-change materials.

BACKGROUND

Stents are commonly placed inside blood vessels in order to widennarrowed or occluded blood vessels and, subsequently, to ensure that theblood vessel remains widened. Heating a stent subsequent to itsimplantation has been shown to prevent restenosis of the blood vessel(i.e., the re-narrowing of a blood vessel after it has been widened).

When a solid material is heated until its melting point, the materialundergoes a phase-change to its liquid state. During the phase-change,the material accumulates a certain amount of heat, which is called thelatent heat of fusion, or the enthalpy change of fusion. The temperatureof the material stays relatively constant when the phase change occurs.When the process is reversed, i.e., when the material undergoes aphase-change from liquid to solid, the accumulated latent heat isreleased.

In oncology, the Warburg effect describes the observation that mostcancer cells predominantly produce energy by glycolysis followed bylactic acid fermentation, rather than by oxidation of pyruvate like mosthealthy cells. The Warburg effect results in cancer cells consuming morethan 20 times the quantity of glucose to produce energy than do healthycells, ceteris paribus.

An article on Wikipedia (18 Jan. 2009) entitled “Fluorodeoxyglucose”states “FDG [Fluorodeoxyglucose] is most commonly used in the medicalimaging modality positron emission tomography (PET): the fluorine in theFDG molecule is chosen to be the positron-emitting radioactive isotopefluorine-18, to produce 18F-FDG. After FDG is injected into a patient, aPET scanner can form images of the distribution of FDG around the body.The images can be assessed by a nuclear medicine physician orradiologist to provide diagnoses of various medical conditions . . .FDG, as a glucose analog, is taken up by high-glucose-using cells suchas brain, kidney, and cancer cells, where phosphorylation prevents theglucose from being released intact. The 2-oxygen in glucose is neededfor further glycolysis, so that (in common with 2-deoxy-D-glucose) FDGcannot be further metabolized in cells, and therefore theFDG-6-phosphate formed does not undergo glycolysis before radioactivedecay. As a result, the distribution of 18F-FDG is a good reflection ofthe distribution of glucose uptake and phosphorylation by cells in thebody.”

A shape-memory alloy is an alloy, such as nitinol orcopper-aluminum-nickel, that has a first shape when it is below a giventemperature (the “transformation temperature”), and that changes toassume a second shape when it is heated to the transformationtemperature.

PCT Publication WO 94/001165 to Gross describes a medicationadministering device includes a housing introducible into a body cavityand of a material insoluble in the body cavity fluids, but formed withan opening covered by a material which is soluble in body cavity fluids.A diaphragm divides the interior of the housing into a medicationchamber including the opening, and a control chamber. An electrolyticcell in the control chamber generates a gas when electrical current ispassed therethrough to deliver medication from the medication chamberthrough the opening into the body cavity at a rate controlled by theelectrical current. The device can be in the form of a pill or capsuleto be taken orally.

US Patent Application Publication 2006/0241747 to Shaoulian describestissue shaping methods and devices. The devices are described as beingadjusted within the body of a patient in a less invasive or non-invasivemanner, such as by applying energy percutaneously or external to thepatient's body. In one example, the device is positioned within thecoronary sinus of the patient so as to effect changes in at least onedimension of the mitral valve annulus. The device is described asincluding a shape memory material that is responsive to changes intemperature and/or exposure to a magnetic field. In one example, theshape memory material is responsive to energy, such as electromagneticor acoustic energy, applied from an energy source located outside thecoronary sinus. A material having enhanced absorption characteristicswith respect to the desired heating energy is also described as beingused to facilitate heating and adjustment of the tissue shaping device.

U.S. patent application Publication 5,545,210 to Hess describes apermanent tissue supporting device, and a method for supporting tissue,wherein a stent-like member comprising a shape-memory alloy ispermanently positioned to support the tissue of a tubular organ of aliving body. The shape-memory alloy of the positioned stent-like memberis in the martensitic state and exhibits a strain on a horizontalplateau of a stress-strain curve of the shape-memory alloy whenpermanently positioned in the tubular organ.

U.S. Pat. No. 6,059,810 to Brown describes a stent for reinforcing avessel wall, the stent being expandable and comprised of a shape memoryalloy which in the normal implanted condition is in the martensiticphase at body temperature, the stent further having a larger parent oraustenitic shape and diameter when heated above its transitiontemperature.

Galil Medical (Yokneam, Israel) manufactures cryotherapy systems.

The following references may be of interest:

U.S. Pat. No. 6,805,711 to Quijano

U.S. Pat. No. 6,451,044 to Naghavi et al.

U.S. Pat. No. 6,323,459 to Maynard

U.S. Pat. No. 6,120,534 to Ruiz

U.S. Pat. No. 5,964,744 to Balbierz

U.S. Pat. No. 5,830,179 to Mikus

U.S. Pat. No. 5,716,410 to Wang

U.S. Pat. No. 5,667,522 to Flomenblit

US Patent Application Publication 2002/0183829 to Doscher et al.

US Patent Application Publication 2004/0253304 to Gross

US Patent Application Publication 2004/0180086 to Ramtoola

United States Patent Application Publication 2005/0055082 to Ben Muvhar

US Patent Application Publication 2005/0288777 to Rhee

US Patent Application Publication 2006/0074479 to Bailey

US Patent Application Publication 2006/0241747 to Shaoulian et al.

US Patent Application Publication 2008/021537 to Ben Muvhar

PCT Publication WO 02/000145 to Diamantopoulos

PCT Publication WO 03/028522 to Ben Muvhar

“Pathologic analysis of photothermal and photomechanical effects oflaser-tissue interactions,” by Thomsen, Photochem Photobiol. 1991 Jun.;53(6): 825-35

“The next generation of cancer treatments may be delivered bynanoparticles,” The Economist, Nov. 6, 2008

“Lipase-catalysed synthesis of glucose fatty acid esters intert-butanol,” by Degn et al., Biotechnology Letters 21: 275-280, 1999

“Optimization of Carbohydrate Fatty Acid Ester Synthesis in OrganicMedia by a Lipase from Candida Antarctica,” by Degn et al.,Biotechnology and Bioengineering, Vol. 74, No. 6, Sep. 20, 2001

“Cancer's Molecular Sweet Tooth and the Warburg Effect,” by Kim et al.,Cancer Res 2006; 66: (18). Sep. 15, 2006

Applied Thermal Engineering, Zalba et al., 23(3), February 2003, pp.251-283

SUMMARY OF THE INVENTION

For some applications of the invention, an element (e.g., a stent) isimplanted within a subject's body. A phase-change material is implantedwithin the subject's body in a vicinity of the element. The phase-changematerial absorbs heat from the element by being heated to itsphase-change temperature. Typically, in response to being heated, thephase-change material absorbs latent heat of fusion, but not all of thephase-change material undergoes a change in phase. For someapplications, at least a portion of the phase-change material undergoesa change in phase (for example, from solid to liquid, or solid to gel).

For some applications, the element is a stent that is implanted inside ablood vessel. When the stent is heated to prevent restenosis of theblood vessel, the phase-change material prevents the stent, and/ortissue surrounding the stent, from overheating, by absorbing heat fromthe stent. For some applications, the phase-change material absorbs heatfrom an implanted element during procedures during which the implantedelement may otherwise overheat. For example, the phase-change materialmay absorb heat from a stent that is implanted inside a subject whilethe subject undergoes an MRI procedure, or another procedure duringwhich the stent is exposed to electromagnetic fields.

For some applications, a portion of a subject's body is heated, forexample, during a medical procedure. A phase-change material is placedwithin the subject's body in a vicinity of the heated portion. Thephase-change material absorbs heat from the vicinity of the heatedportion.

For some applications, a portion of the subject's body is cooled, forexample, a portion of the subject's body is cryoablated (e.g., using acryoablation system manufactured by Galil Medical). A phase-changematerial is implanted in tissue surrounding the portion. Thephase-change material releases latent heat energy by being cooled to itsphase change temperature (e.g., the transition temperature from liquidto solid, or from gel to solid), thereby preventing damage to thesurrounding tissue.

For some applications of the present invention, a system is provided forrupturing cancer cells of a subject, the subject having cancer cells andhealthy cells. Clusters of phase-change molecules are coupled torespective first molecules (e.g., respective molecules of glucose). Aplurality of the first molecules are administered to the subject andcouple to the cancer cells to a greater extent than to the healthycells. Typically, the first molecule is selected such that, by virtue ofthe Warburg effect, the first molecule couples to the cancer cells to agreater extent than to the healthy cells. For example, respective firstmolecules may be glucose molecules, and more than twenty times as manyglucose molecules may become coupled to the cancer cells as becomecoupled to the healthy cells.

While the first molecules are coupled to the cancer cells, energy istransmitted toward the clusters of phase-change molecules. In responseto the energy striking the clusters of phase-change molecules, thetemperature of the region in which the phase-change change molecules aredisposed rises, but does not rise above the phase-change temperature ofthe phase-change molecules. This is because, at the phase-changetemperature, the heat that is transmitted toward the region is absorbedby the phase-change molecules as latent heat. The heating of thephase-change molecules typically heats the cancer cells, thereby killingthe cancer cells. In some circumstances, the absorption of the energy bythe phase-change molecules causes the phase-change molecules to vibrate,thereby rupturing the membranes of the cancer cells. For someapplications, energy is transmitted toward the clusters at the resonancefrequency of the phase-change molecules, in order to enhance theabsorption of energy by the phase-change molecules.

For some applications of the present invention, an implantable elementis implanted inside a subject's body. The element includes ashape-memory material having a transformation temperature. Theimplantable element performs a first therapeutic function with respectto a portion of the subject's body when the shape-memory material is ina first shape. An energy applicator changes the shape-memory materialfrom the first shape to a second shape, by raising a temperature of theshape-memory material to the transformation temperature of theshape-memory material. When the shape-memory material is in the secondshape, the implantable element performs a second therapeutic functionwith respect to the portion, the second therapeutic function beingqualitatively different from the first therapeutic function.

For some applications, the implantable element comprises a stent. Thestent is implanted into a blood vessel of the subject, which istypically a narrowed blood vessel. While the stent is in a firstconfiguration, it opens the blood vessel by supporting the inner wallsof the blood vessel. Subsequently, the stent is heated and the shape ofthe stent changes to the shape of a venturi tube. The venturi-tubeshaped stent causes the generation of new blood vessels in the vicinityof the blood vessel in which the stent is disposed, as describedhereinbelow, and/or in accordance with the techniques described in PCTPublication WO 03/028522 to Ben Muvhar, which is incorporated herein byreference.

There is therefore provided, in accordance with some applications of thepresent invention, apparatus, including:

an implantable element configured to be implanted within a body of asubject; and

a phase-change material configured:

to be implanted within the subject's body in a vicinity of the element,and

to absorb heat from the element by absorbing latent heat of fusionresulting from a phase-change of the phase-change material selected fromthe group consisting of: wax to liquid, solid to liquid, solid to gel,and gel to liquid, in response to the element being heated.

For some applications, less than all of the phase-change material isconfigured to undergo the selected phase change, in response to theelement being heated.

For some applications, the phase-change material includes paraffin.

For some applications, the phase-change material includes an organicphase-change material.

For some applications, the implantable element includes a stent.

For some applications, the phase-change material is configured to absorbheat from the element in response to the element being heated by beingexposed to an electromagnetic field.

For some applications, the phase-change material has a phase-changetemperature of 4.5 C to 145 C.

For some applications, the phase-change material has a phase-changetemperature of 45 C to 60 C.

For some applications, the phase-change material has a phase-changetemperature of 60 C to 80 C.

For some applications, the phase-change material is configured to beimplanted in a separate implantation step from implantation of theimplantable element.

For some applications, the phase-change material is configured not to beattached to the implantable element when the implantable element and thephase-change material are implanted within the subject's body.

For some applications, the phase-change material and the implantableelement are configured to be implanted in a single implantation step.

For some applications, the phase-change material includes a coating thatcoats the implantable element.

For some applications, the phase-change material is disposed within theimplantable element.

For some applications, the implantable element defines a hollow volume,and the phase-change material is disposed inside the hollow volume.

There is further provided, in accordance with some applications of thepresent invention, a method, including:

placing a phase-change material within a body of a subject; and

causing the phase-change material within the subject's body to absorblatent heat of fusion resulting from a phase-change of the phase-changematerial selected from the group consisting of: wax to liquid, solid toliquid, solid to gel, and gel to liquid, by heating the phase-changematerial.

For some applications, causing the phase-change material to absorb thelatent heat of fusion includes causing less than all of the phase-changematerial to undergo the selected phase change, by heating thephase-change material.

For some applications, causing the phase-change material to absorb thelatent heat of fusion includes causing the phase-change material toabsorb heat from a portion of the subject's body in a vicinity of thephase-change material.

There is further provided, in accordance with some applications of thepresent invention, apparatus, including:

a heating device configured to heat a portion of a body of a subject;and

a phase-change material configured:

-   -   to be placed within the subject's body in a vicinity of the        portion, and    -   to absorb heat from the vicinity of the portion by absorbing        latent heat of fusion resulting from a phase-change of the        phase-change material selected from the group consisting of: wax        to liquid, solid to liquid, solid to gel, and gel to liquid, in        response to the portion of the subject's body being heated.

For some applications, less than all of the phase-change material isconfigured to undergo the selected phase change, in response to theportion being heated.

For some applications, the phase-change material includes paraffin.

For some applications, the phase-change material includes an organicphase-change material.

For some applications, the phase-change material includes a gelconfigured to be injected into the subject's body in the vicinity of theportion.

For some applications, the phase-change material includes a solid pelletconfigured to be injected into the subject's body in the vicinity of theportion.

For some applications, the phase-change material has a phase-changetemperature of 4.5 C to 145 C.

For some applications, the phase-change material has a phase-changetemperature of 45 C to 60 C.

For some applications, the phase-change material has a phase-changetemperature of 60 C to 80 C.

For some applications, the apparatus further includes an energyabsorbing element configured to be implanted within the portion and toabsorb energy from the heating device.

For some applications, the energy absorbing element includes a carboncylinder having a diameter that is at least 0.9 mm.

For some applications, the energy absorbing element includes abiocompatible metal.

There is further provided, in accordance with some applications of thepresent invention, apparatus, including:

an implantable element configured to be implanted within a body of asubject; and

a phase-change material configured:

-   -   to be implanted within the subject's body in a vicinity of the        element, and    -   to release latent heat of fusion resulting from a phase-change        of the phase-change material selected from the group consisting        of: liquid to wax, liquid to solid, gel to solid, and liquid to        gel, in response to the element being cooled.

There is additionally provided, in accordance with some applications ofthe present invention, a method, including:

placing a phase-change material within a body of a subject; and

causing the phase-change material within the subject's body to releaselatent heat of fusion resulting from a phase-change of the phase-changematerial selected from the group consisting of: liquid to wax, liquid tosolid, gel to solid, and liquid to gel, by cooling the phase-changematerial.

There is further provided, in accordance with some applications of thepresent invention, apparatus for killing cancer cells of a subject, thesubject having cancer cells and healthy cells, the apparatus including:

a plurality of first molecules configured to be coupled to the cancercells to a greater extent than to the healthy cells, in response tobeing administered to the subject;

a plurality of clusters of phase-change molecules, each of the clusterscoupled to a respective one of the first molecules; and

an energy transmission unit, configured to kill cancer cells coupled tothe first molecules by heating the cancer cells, by transmitting energytoward the clusters that selectively heats the clusters.

For some applications, the energy transmission unit is configured torupture membranes of the cancer cells by heating the cancer cells.

For some applications, the energy transmission unit is configured toheat the clusters to a melting temperature of the phase-changemolecules, and the phase-change molecules are configured to absorblatent heat of fusion in response to the clusters being heated.

For some applications, the energy transmission unit is configured totransmit energy at a resonance frequency of the phase-change molecules.

For some applications, the phase-change molecules include paraffinmolecules.

For some applications, the phase-change molecules include organicphase-change molecules.

For some applications, the energy transmission unit is configured toheat the clusters such that less than all of the phase-change moleculesin each of the clusters undergo the selected phase change, in responseto the clusters being heated.

For some applications, the first molecules include glucose molecules.

For some applications, the clusters of phase-change molecules have aphase-change temperature between 60 and 80 C.

For some applications, the clusters of phase-change molecules have aphase-change temperature between 45 and 60 C.

For some applications, the energy transmission unit is configured toheat the clusters such that a temperature of the clusters does not riseabove a phase-change temperature of the phase-change molecules, inresponse to the clusters being heated.

For some applications, the energy transmission unit is configured todiscontinue the transmission of the energy in response to an indicationof the temperature of the clusters.

For some applications, the energy transmission unit is configured tosense a temperature of the clusters and to discontinue the transmissionof the energy in response to the sensed temperature.

For some applications, the energy transmission unit is configured todiscontinue transmission of the energy in response to a duration oftransmission of the energy.

There is further provided, in accordance with some applications of thepresent invention, a method for killing cancer cells of a subject, thesubject having the cancer cells and healthy cells, the method including:

administering to the subject a plurality of first molecules, each of thefirst molecules having a cluster of phase-change molecules coupledthereto, the first molecules being configured to be coupled to thecancer cells to a greater extent than to the healthy cells; and

killing the cancer cells by heating the cancer cells, by transmittingenergy toward the clusters that selectively heats the clusters.

For some applications, transmitting energy toward the clusters includesirradiating multiple sites to which the cancer cells may havemetastasized.

For some applications, the method further includes imaging the subjectwhile transmitting energy toward the clusters.

For some applications, imaging the subject includes imaging the cancercells using a heat-sensitive imaging protocol.

There is therefore provided, in accordance with some applications of thepresent invention, apparatus for use with a portion of a body of asubject, including:

an implantable element, including a shape-memory material having atransformation temperature, the implantable element configured to beimplanted in the portion, and to perform a first therapeutic functionwith respect to the portion when the shape-memory material is in a firstshape, and while the implantable element is implanted in the portion;and

an energy applicator, configured to change the shape-memory materialfrom the first shape to a second shape, by raising a temperature of theshape-memory material to the transformation temperature,

the implantable element being configured to perform a second therapeuticfunction with respect to the portion when the shape-memory material isin the second shape, while the implantable element is implanted in theportion, the second therapeutic function being qualitatively differentfrom the first therapeutic function.

For some applications, the implantable element is shaped as acylindrical stent when the shape-memory material is in the first shape.

For some applications, the implantable element is shaped as a venturitube when the shape-memory material is in the second shape.

There is further provided, in accordance with some applications of thepresent invention, a method for use with a portion of a body of asubject, including:

implanting an implantable element in the portion;

performing a first therapeutic function with respect to the portionusing the implantable element while the implantable element is implantedin the portion, the implantable element including a shape-memorymaterial that has a transformation temperature, the shape-memorymaterial being in a first shape during the performing of the firsttherapeutic function;

changing the shape-memory material from the first shape to a secondshape by raising a temperature of the shape-memory material to thetransformation temperature; and

performing a second therapeutic function with respect to the portionusing the implantable element, while the implantable element isimplanted in the portion, and when the shape-memory material is in thesecond shape.

For some applications, performing the first therapeutic functionincludes opening a blood vessel of the subject, the implantable elementbeing shaped as a cylindrical stent when the shape-memory material is inthe first shape thereof.

For some applications, performing the second therapeutic functionincludes increasing blood pressure in a portion of the blood vessel thatis proximal to the implantable element, the implantable element beingshaped as a venturi tube when the shape-memory material is in the secondshape thereof.

There is additionally provided, in accordance with some applications ofthe present invention, a method for use with a portion of a body of asubject, including:

implanting an implantable element in the portion;

performing a first therapeutic function with respect to the portionusing the implantable element, while the implantable element isimplanted in the portion, the implantable element being in a firstmechanical configuration during the performing of the first therapeuticfunction;

changing the implantable element from the first mechanical configurationto a second mechanical configuration by raising a temperature of theimplantable element; and

performing a second therapeutic function with respect to the portionusing the implantable element, while the implantable element isimplanted in the portion, and when the implantable element material isin the second mechanical configuration.

There is further provided, in accordance with some applications of thepresent invention, an implantable pump for dispensing a drug, including:

a drug chamber configured to contain a drug; and

a shape-memory material configured to force at least some of the drugout of the pump, by expanding, by being heated to a given temperature.

For some applications, the shape-change material is configured to expandby being heated to a temperature of 40-60 C.

For some applications, the drug includes a chemotherapy agent, and thedrug chamber is configured to contain the chemotherapy agent.

There is additionally provided, in accordance with some applications ofthe present invention, a method, including:

implanting a drug pump inside a body of a subject, the pump including adrug chamber that is configured to contain a drug; and

forcing at least a portion of the drug out of the drug chamber byexpanding a shape-memory material that has a transformation temperature,by heating the shape-memory material to the transformation temperaturefor a first given time period.

For some applications, the method further includes forcing a furtherportion of the drug out of the drug chamber by further expanding theshape-memory material by heating the shape-memory material to thetransformation temperature for a second given time period.

For some applications, heating the shape-memory material to thetransformation temperature includes heating the shape-memory material toa temperature of 40-60 C.

For some applications, the medication includes a chemotherapy agent, andforcing the medication out of the drug chamber includes forcing thechemotherapy agent out of the drug chamber.

The present invention will be more fully understood from the followingdetailed description of embodiments thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic illustration of a phase-change material inside ahollow implantable element, in accordance with some applications of thepresent invention;

FIG. 1B is a schematic illustration of a phase-change material implantedin a vicinity of a portion of a subject's body that is being heated, inaccordance with some applications of the present invention;

FIG. 2A is a schematic illustration of a cluster of phase-changemolecules coupled to a glucose molecule, near a cancer cell, inaccordance with some applications of the present invention;

FIG. 2B is a schematic illustration of the cluster of phase-changemolecules coupled to the membrane of a cancer cell via the glucosemolecule, in accordance with some applications of the present invention;

FIG. 3 is a graph showing experimental results of five pieces of tissuethat were heated in a control experiment;

FIG. 4 is a graph showing experimental results of four pieces of tissuethat were injected with phase-change materials and were heated, inaccordance with some applications of the present invention;

FIG. 5 is a graph showing further experimental results of four pieces oftissue that were injected with phase-change materials and were heated,in accordance with some applications of the present invention.

FIG. 6 is a schematic illustration of an implantable element implantedinside a blood vessel of a subject;

FIG. 7A is a schematic illustration of the implantable element in afirst configuration, in accordance with some applications of the presentinvention;

FIG. 7B is a schematic illustration of the implantable element in asecond configuration, in accordance with some applications of thepresent invention; and

FIGS. 8A-B are schematic illustrations of a portion of a drug pumphaving an expansible shape-memory portion, in accordance with someapplications of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is now made to FIG. 1A, which is a schematic illustration of aphase-change material 22 inside an implantable element 20, in accordancewith some applications of the present invention. The phase-changematerial absorbs heat from the element by being heated to thephase-change temperature of the phase-change material and absorbinglatent heat energy.

For some applications, implantable element 20 is a stent, andphase-change material 22 is disposed inside the stent. For example, thestent may be shaped as a hollow tube, or may be shaped in a differentshape that allows the stent to contain the phase-change materialtherein. Alternatively or additionally, the phase-change material coatsthe implantable element. Typically, for applications in which thephase-change material is inside the implantable element, and/or coatsthe implantable element, phase-change material 22 and implantableelement 20 are implanted within a subject's body in a singleimplantation step. For some applications, the phase-change material isnot attached to the implantable element when the phase-change materialand the implantable element are within the subject's body. For example,the phase-change material may be implanted in tissue that is at adistance of several millimeters or micrometers from the implantableelement, and the phase-change material may reduce heating of the tissuewhen the implantable element is heated. For some applications, thephase-change material is implanted in a separate implantation step fromthe implantation of the implantable element.

For some applications, one or more of the phase-change materials thatappear (hereinbelow) in Table 1 and/or in Table 2 are used asphase-change material 22. Typically, a phase-change material is selectedas the phase-change material, on the basis of the phase-changetemperature of the phase-change material. For example, if it is desiredto heat implantable element 20 to a temperature of 42 C, paraffin havinga molecule length of 16 carbon atoms (C16) may be selected, inaccordance with the data in Table 1 (which is extracted from Zalba etal., Applied Thermal Engineering, 23(3), February 2003, pp. 251-283).When the element is heated to 42 C, the selected phase-change materialabsorbs energy as it absorbs latent heat of fusion. While thephase-change material absorbs energy, the heating of the element and/orthe surrounding tissue is inhibited. For some applications, othermelting temperatures and corresponding materials are used.

TABLE 1 Melting temperatures of paraffin molecules   Compound   Meltingtemperature (° C.)${Heat}\mspace{14mu}{of}\mspace{14mu}{fusion}\mspace{14mu}\left( \frac{Kj}{Kg} \right)$Paraffin C16-C28 42-44 189   Paraffin C20-C33 48-50 189   ParaffinC22-C45 58-60 189   Paraffin wax  64 173.6 Paraffin C28-C50 66-68 189  Paraffin RT40  43 181   Paraffin RT50  54 195   Paraffin RT65  64 207  Paraffin RT80  79 209   Paraffin RT90  90 197   Paraffin RT110 112 213  

TABLE 2 Melting temperature of organic phase-change materials:          Compound         Melting Temperature ?° C.? Heat of Fusion$\begin{matrix}? \\? \\? \\?\end{matrix}\frac{Kj}{Kg}\begin{matrix}? \\? \\? \\?\end{matrix}$ Paraffin C14 4.5 165 Paraffin C15-C16 8 153 PolyglycolE400 8 99.6 Dimethyl-sulfoxide (DMS) 16.5 85.7 Paraffin C16-C18 20-22152 Polyglycol E600 22 189 Paraffin C13-C24 22-24 189 1-Dodecanol 26 200Paraffin C18 28 244 1-Tetradecanol 26 200 Paraffin C16-C28 42-44 189Paraffin C20-C33 48-50 189 Paraffin C22-C45 58-60 189 Paraffin Wax 64173.6 Polyglycol E6000 66 190 Paraffin C28-C30 66-68 189 Biphenyl 71119.2 Propionamide 79 168.2 Naphthalene 80 147.7 Erythritol 118 339.8HDPE 100-150 200 Trans-1,4-polybutadiene 145 144 (TPB)

For some applications, one or more of the following organic phase-changematerials is used for phase-change material 22: crude oil, paraffinproduced by the Fischer-Tropsch process, and an organic material havingsaturated, unsaturated, straight, or branched carbon chain molecules.The phase-change material may include, for example, trilaurin,trimyristin, tripalmitin, tristearin, and/or any suitable type ofparaffin or paraffin wax.

The phase-change temperature (e.g., the melting temperature) of thephase-change material is typically 4.5 C to 145 C, e.g., 45 C to 60 C,or 60 C to 80 C. For some applications, the phase-change material hasrelatively low thermal conductivity, and is arranged to have a largesurface area to overcome the low thermal conductivity and increase theflow of heat into the phase-change material.

For some applications, when coupling phase-change material 22 toimplantable element 20, and/or when implanting the phase-changematerial, it is assumed that the phase-change material will undergothermal expansion, and the coupling and/or implantation is performedaccordingly. For example, if the phase-change material is disposedinside a hollow volume inside a stent (as shown in FIG. 1A), 10 percentof the hollow volume may be left empty to allow for the thermalexpansion of the phase-change material inside the hollow volume.Alternatively, the phase-change material is disposed inside a hollowvolume inside a stent (as shown in FIG. 1A), and the stent ishermetically sealed, in order to reduce or prevent expansion of thephase-change material.

Reference is now made to FIG. 1B, which is a schematic illustration ofphase-change material 22 implanted in a vicinity of a portion 32 of asubject's body 34 that is being heated by a heating device 30 (e.g., anultrasound transducer), in accordance with some applications of thepresent invention. For some applications, the phase-change material isplaced within the subject's body in the vicinity of portion 32. Duringthe heating of portion 32, the phase-change material absorbs latent heatof fusion from tissue in the vicinity of the portion by being heated tothe phase-change temperature of the phase-change material. Typically,one of the phase-change materials that appears in Table 1, or anotherphase-change material is selected, based upon the temperature to whichportion 32 is heated.

For some applications, portion 32 includes cancerous tissue which isheated by heating device 30 to denature the tissue. The absorption ofheat near other tissue in the vicinity of portion 32 prevents the othertissue from overheating and becoming denatured. For some applications,the temperature to which portion 32 is heated depends on the nature ofportion 32. For example, denaturing tissue of the kidney, which has ahigh level of perfusion, requires heating the tissue to a highertemperature than would be required in order to denature tissue of thelungs.

For some applications, phase-change material 22 is injected into tissuein the vicinity of portion 32, and/or in the vicinity of implantableelement 20, in the form of pellets and/or gel.

For some applications, an energy absorbing element 36, such as carbon orgraphite, is inserted into portion 32 to facilitate the heating of thetissue by efficiently absorbing energy from heating device 30 andundergoing an elevation in temperature.

For some applications, implantable element 20 is coupled to phase-changematerial 22, as described hereinabove. The implantable element and thephase-change material are implanted in the vicinity of portion 32.Heating device 30 heats the implantable element, and, simultaneously,the phase-change material prevents the temperature of the implantableelement from rising above a given temperature. For some applications,implanting the implantable element at a specific implantation site withrespect to portion 32 facilitates the directing of the heat toward theportion.

Reference is now made to FIG. 2A, which is a schematic illustration of acancer-treatment substance that includes a sugar molecule, e.g., aglucose molecule 40, coupled to a cluster 42 of phase-change molecules,in accordance with some applications of the present invention. Thesubstance is administered to the subject, for example, orally, or byinjection. The substance is configured such that cancer cells 44 absorbmore of the substance than healthy cells of the surrounding tissue, dueto the preferential uptake of the glucose molecules by the cancer cells.The preferential uptake of glucose molecules by cancer cells is based onthe Warburg effect, described hereinabove in the Background, and asdescribed in “Cancer's Molecular Sweet Tooth and the Warburg Effect,” byKim et al., Cancer Res 2006; 66: (18). Sep. 15, 2006, which isincorporated herein by reference. (The principle of cancer cellspreferentially uptaking glucose molecules forms the basis of certainPET-CT imaging protocols, as described in the Wikipedia article entitled“Fluorodeoxyglucose,” which is incorporated herein by reference.)

For some applications, techniques that are known in the art are used forcoupling the phase-change molecules to glucose molecule 40. For example,techniques may be used that are based on techniques described in thefollowing articles, which are incorporated herein by reference: (a)“Lipase-catalysed synthesis of glucose fatty acid esters intert-butanol,” by Degn et al., Biotechnology Letters 21: 275-280, 1999,and (b) “Optimization of Carbohydrate Fatty Acid Ester Synthesis inOrganic Media by a Lipase from Candida Antarctica,” by Degn et al.,Biotechnology and Bioengineering, Vol. 74, No. 6, Sep. 20, 2001.

Reference is now made to FIG. 2B, which is a schematic illustration ofcluster 42 of phase-change molecules coupled to membrane 46 of cancercell 44, via glucose molecule 40, in accordance with some applicationsof the present invention. Typically, glucose molecule 40 passes at leastpartially through membrane 46 of cancer cell 44, via a glucose channel48. Further typically, the cluster of phase-change molecules is unableto pass through the cell membrane, but since it remains coupled to theglucose molecule, it becomes coupled to the cell membrane. (Although,FIG. 2B shows that phase-change molecule 42 is unable to pass throughglucose channel 48 due to the size of cluster 42 of phase-changemolecules, the scope of the present invention includes using a clusterof phase-change molecules that is unable to pass through the glucosechannel for another reason.)

While cluster 42 of phase-change molecules is coupled to membrane 46,energy is directed toward cancer cell 44. For example, an energytransmission unit 50 irradiates a region of the body in which cancercell 44 is located. For some applications, the cancer cell is heated tothe phase-change temperature of the phase-change molecules. For someapplications, the phase-change molecules absorb heat without all of themolecules changing phase (e.g., from solid to liquid), the heat beingabsorbed as latent heat of fusion of the phase change. Typically, thetemperature of the phase-change molecules and the vicinity of thephase-change molecules remains substantially constant once thephase-change molecules have been heated to the phase-change temperature.Further typically, the energy transmission unit does not heat thecluster to a temperature that is greater than the phase-changetemperature. For some applications, the energy transmission unitdiscontinues the transmission of energy in response to an indication ofthe temperature of the clusters. For example, the energy transmissionunit may sense a temperature of the clusters using known techniques, anddiscontinue the transmission of the energy in response to the sensedtemperature. Alternatively or additionally, the energy transmission unitdiscontinues transmission of the energy in response to a duration oftransmission of the energy, i.e., the unit ceases to transmit energyafter a given time period.

Typically, the heating of the phase-change molecules heats the cancercell, thereby killing the cancer cell. For some applications, the cancercell is irradiated at a frequency that is the resonance frequency of thephase-change molecule. For some applications, the heating of cluster 42causes the cluster to vibrate. The vibration of cluster 42, while thecluster is coupled to cell membrane 46, causes the cancer cell membraneto rupture, thereby killing the cancer cell.

For some applications, the effect of the heating of the phase-changemolecules on the cancer is in accordance with Table 3, which appears inan article by Thomsen, entitled “Pathologic analysis of photothermal andphotomechanical effects of laser-tissue interactions” (PhotochemPhotobiol. 1991 June; 53(6): 825-35), which is incorporated herein byreference:

TABLE 3 Histopathological effect of heating on cells Thermal Temperaturedamage of onset: mechanism range (° C.) Heating times Histopathologyeffect Low- 40-45 Hours Reversible cell injury: temperature heatinactivation of damage enzymes; metabolic accumulation accelerationprocesses Low 40+ Hours to minutes Edema and hyperemia  43-45+ HoursCell death: deactivation of enzymes Unknown Unknown Cell shrinkage andhyperchromasia 43+ Minutes Birefringence loss in frozen and thawedmyocardium 45+ Minutes to Thermal denaturization seconds of structuralproteins in fresh tissue Unknown Unknown Cell membrane rupture 50-90Minutes to Hyalinization of seconds collagen 54-78 3.6 to 0.4 secondsBirefringence loss in laser irradiated fresh myocardium  55-95+ MinutesBirefringence changes in collagen Water 100 ?  Seconds Extracellularvacuole dominated formation. Rupture of processes vacuoles, “popcorn”effect 100-200 Seconds to Tissue ablation by milliseconds explosivefragmentation Over 200 Seconds to Tissue ablation picoseconds

Typically, as stated hereinabove, the region of the subject's body inwhich cancer cells 44 are located is heated to the phase-changetemperature of the phase-change molecules. For some applications,phase-change molecules having a phase-change temperature of 45 C to 60C, or 60 C to 80 C are used in cluster 42. Further typically, during theheating, the healthy cells do not absorb as much heat as thephase-change molecules, because the radiation is selected to be at theresonance frequency of the phase-change material molecules, which arepredominantly in contact with or very near to cancer cells.

For some applications, when it is suspected that cancer tissue hasmetastasized, the cancer-treatment substance is administered to thesubject. Energy is then directed toward regions of the subject's body towhich the cancer may have metastasized. If cancer cells are present inthe region, the phase-change material molecules preferentially absorbthe energy, and the cancer cells are killed, while the healthy cellsremain generally intact. (Use of these applications may include killingsome healthy cells, along with killing a large number of cancer cells.)For some applications, when it is suspected that cancer tissue hasmetastasized, the subject's whole body is irradiated with the energythat is preferentially absorbed by the clusters, subsequent toadministering the substance to the subject. As described hereinabove,due the coupling of the phase-change molecules to the cancer cells, thecancer cells are selectively heated and are killed.

For some applications, the methods described herein are applied to thesubject while imaging the subject, for example, using CT and/or MRIimaging protocols. For some applications, the substance is administeredto the subject, and the subject's body (or a region thereof) isirradiated with the energy that is preferentially absorbed by theclusters, as described herein. While the subject's body is irradiated,the subject's body is imaged using a heat-sensitive imaging protocol(for example, using MRI) to detect which regions of the subject's body(including cancer cells) have been heated.

In accordance with respective applications of the invention, selectioncriteria for selecting phase-change molecules for use in cluster 42include thermodynamic, kinetic, and chemical properties of thephase-change molecules. For some applications, the phase-changemolecules are selected to have given thermodynamic properties, such as amelting temperature in the desired operating temperature range, a highlatent heat of fusion per unit volume, high specific heat, high density,high thermal conductivity, small volume changes on phase transformation,small vapor pressure at operating temperatures, and/or congruentmelting. For some applications, the phase-change molecules are selectedto have given kinetic properties, such as a high nucleation rate, and/ora high rate of crystal growth. For some applications, the phase-changemolecules are selected to have given chemical properties, such aschemical stability, reversibility of the phase-change cycle withoutdegradation of the molecules after a large number of phase-changecycles, non-corrosiveness, and/or non-toxicity.

For some applications, organic phase-change material molecules are usedfor cluster 42. For example, paraffin and/or fatty acid molecules may beused in cluster 42. For some applications, organic molecules are used incluster 42 because the organic phase change-molecules freeze withoutsubstantial super cooling, are able to melt congruently, haveself-nucleating properties, do not segregate, are chemically stable,have a high heat of fusion, and/or for a different reason.

For some applications, one or more of the following phase-changemolecules are used in cluster 42: Octadecane (CAS Number 593-45-3),Laurie acid (CAS No: 143-07-7), Myristic acid (CAS No: 544-63-8),Palmitic acid (CAS No: 57-10-3), Heptadecanoic acid (CAS No: 506-12-7),Stearic acid (CAS No: 57-11-4), Arachidic acid (CAS No: 506-30-9),Behenic acid (Cas No: 112-85-6) Trimethylolethane (CAS No: 77-85-0),Stearamine (Octadecylamine) (Sigma-74750), Cetylamine (Hexadecylamine)(Sigma-445312).

For some applications, one or more of the phase-change materials thatappear in Table 1, and/or in Table 2 (both which tables are shownhereinabove), are used as the phase-change material of cluster 42.Typically, a phase-change material is selected as the phase-changematerial, on the basis of the phase change temperature of thephase-change material. For some applications, other melting temperaturesand corresponding materials are used.

For some applications, one or more of the following organic phase-changematerials is used for phase-change material 42: crude oil, paraffinproduced by the Fischer-Tropsch process, and an organic material havingsaturated, unsaturated, straight, or branched carbon chain molecules.The phase-change material may include, for example, trilaurin,trimyristin, tripalmitin, tristearin, and/or any suitable type ofparaffin or paraffm wax.

The melting temperature of the phase-change material is typically 45 Cto 60 C, or 60 C to 80 C. The phase change which the phase changematerial undergoes, is typically solid to liquid, solid to gel, or gelto liquid.

Reference is now made to FIG. 3, which is a graph showing experimentalresults of five pieces of tissue that were heated in a controlexperiment, conducted in accordance with some applications of thepresent invention. Five pieces of tissue, each weighing 13 grams, werecut from either turkey liver, chicken chest, or calf liver. The piecesof tissue were each mounted on a polystyrene board, using mounting pins,at a distance of 55 mm from an RF generator. The RF generator irradiatedeach piece of tissue for several time intervals: 30 sec, 50 sec, 80 sec,and 100 sec. The temperature of each of the pieces of tissue wasmeasured immediately after the tissue was irradiated, using a k-typethermocouple. The maximum temperature in the tissue following theirradiation of the tissue is shown in Table 4, and is plotted on thegraph of FIG. 3. The ambient temperature was 24.2 C-25 C. Theirradiation of the pieces was done in accordance with the followingprotocol:

-   -   Piece 1—A 40 mm reflector was mounted on the RF generator in        order to concentrate the RF energy on a specific area, and, in        doing so, reduce damage to peripheral portions of the tissue.    -   Piece 2—A 30 mm reflector was mounted on the RF generator.    -   Piece 3—No reflector was mounted on the RF generator.    -   Piece 4—No reflector was mounted on the RF generator. Carbon        cylinders, each cylinder having a diameter of 0.9 mm and a        length of 20 mm to 40 mm, were inserted into the tissue at        intervals of 10 mm.    -   Piece 5—No reflector was mounted on the RF generator. Carbon        cylinders, each cylinder having a diameter of 2 mm and a length        of 20 mm to 40 mm, were inserted into the tissue at intervals of        10 mm.

TABLE 4 Initial and final temperatures of control group INITIAL MAXIMUMFINAL TIME INTERVAL TEMPERATURE TEMPERATURE PIECE (s) (° C.) (° C.) 1 3024.0 24.8 1 50 24.8 25.4 1 80 25.4 38.4 1 100 23.7 47.5 2 30 19.8 23.1 250 23.1 30.4 2 80 28.7 42.2 2 100 35.6 50.3 3 30 25.5 27.4 3 50 28.634.6 3 80 32.7 66.3 3 100 55.0 95.8 4 30 23.3 36.3 4 50 35.2 48.9 4 8047.5 73.2 4 100 71.2 122.3 5 30 23.8 37.9 5 50 37.3 50.3 5 80 48.7 85.85 100 73.2 143.4

As is seen in FIG. 3, use of carbon cylinders in the tissue acceleratesthe heating of the tissue, and a 2 mm diameter cylinder causes fasterheating than a 0.9 mm diameter cylinder. It is noted that experimentswere conducted on the control group, in which smaller carbon cylinders,having diameters of 0.3 mm, 0.5mm, and 0.7 mm were inserted into thetissue and the tissue was heated. The smaller carbon cylinders wereobserved to have little effect on the heating of the tissue, indicatingthat carbon cylinders that are smaller than a minimum size (e.g., 0.9 mmin diameter) are not good RF energy absorbers when placed inside tissue.In addition, use of a reflector retards heating of the tissue, and alarger reflector retards the heating more than a smaller reflector.

Reference is now made to FIG. 4, which is a graph showing experimentalresults of four pieces of tissue that were injected with phase-changematerials and were heated, in accordance with some applications of thepresent invention. Four pieces of tissue, each weighing 13 grams, werecut from either turkey liver, chicken chest, or calf liver. The piecesof tissue were each mounted on a polystyrene board, using mounting pins,at a distance of 55 mm from an RF generator. A 40 mm reflector wasmounted on the RF generator and the generator irradiated each piece oftissue for several time intervals: 30 sec, 50, sec, 80 sec, 100 sec, and180 sec. The maximum temperature of the tissue following the irradiationof the tissue was measured using a k-type thermocouple, and the resultsshown in Table 5, and are plotted on the graph of FIG. 4. The ambienttemperature was 24.2 C-25 C. The irradiation of the pieces was done inaccordance with the following protocol:

Piece 1—The piece was injected with 5 cc of a trilaurin-based mixture,comprising 0.8 g of trilaurin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200, and 20 g of water.

Piece 2—The piece was injected with 5 cc of a trimyristin-based mixture,comprising 0.8 g of trimyristin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200, and 20 g water.

Piece 3—The piece was injected with 5 cc of a tripalmitin-based mixture,comprising 0.8 g of tripalmitin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200, and 20 g of water.

Piece 4—The piece was injected with 5 cc of a tristearin-based mixture,comprising 0.8 g of tristearin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200 and 20 g water.

TABLE 5 Initial and final temperatures of test group INITIAL MAXIMUMFINAL TIME INTERVAL TEMPERATURE TEMPERATURE PIECE (s) (° C.) (° C.) 1 3024.5 29.2 1 50 28.5 35.4 1 80 34.2 41.8 1 100 40.6 45.7 1 180 44.2 45.72 30 24.8 29.7 2 50 29.1 35.2 2 80 33.9 42.7 2 100 41.1 55.2 2 180 54.755.2 3 30 25.0 31.1 3 50 29.8 36.9 3 80 35.6 44.3 3 100 43.4 65.4 3 18063.2 65.4 4 30 28.6 35.9 4 50 34.6 42.1 4 80 40.3 49.9 4 100 49.2 75 4180 74.1 75

Use of phase-change materials is seen in FIG. 4 to produce prolongedperiods of stable maximum tissue temperature during continuedapplication of energy.

Reference is now made to FIG. 5, which is a graph showing experimentalresults of four pieces of tissue that were injected with phase-changematerials and into which carbon cylinders were inserted, in accordancewith some applications of the present invention. Four pieces of tissue,each weighing 13 grams, were cut from either turkey liver, chickenchest, or calf liver. Carbon cylinders, each cylinder having a diameterof 0.9 mm and a length of 20 mm to 40 mm were inserted into each of thepieces of tissue at intervals of 10 mm. The pieces of tissue were eachmounted on a polystyrene board, using mounting pins, at a distance of 55mm from an RF generator. A 40 mm reflector was mounted on the RFgenerator. Each of the pieces of tissue was heated for several timeintervals. The maximum temperature measured within each of the pieces oftissue following each of these time intervals was measured using ak-type thermocouple, and is shown in Table 6, and plotted on the graphof FIG. 5. The ambient temperature was 24.2 C-25 C. The irradiation ofthe pieces was done in accordance with the following protocol:

Piece 1—The piece was injected with 5 cc of a trilaurin-based mixture,comprising 0.8 g of trilaurin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200, and 20 g of water. The piece was heated for time intervalsof 30 sec, 50 sec, and 180 sec.

Piece 2—The piece was injected with 5 cc of a trimyristin-based mixture,comprising 0.8 g of trimyristin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200, and 20 g water. The piece was heated for time intervals of30 sec, 50 sec, and 180 sec.

Piece 3—The piece was injected with 5 cc of a tripalmitin-based mixture,comprising 0.8 g of tripalmitin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200, and 20 g of water. The piece was heated for time intervalsof 30 sec, 50 sec, 80 sec, and 180 sec.

Piece 4—The piece was injected with 5 cc of a tristearin-based mixture,comprising 0.8 g of tristearin, 0.1 g of Tween 80, 0.16 g of lecithinEpikuron 200 and 20 g water. The piece was heated for time intervals of30 sec, 50 sec, 80 sec, 100 sec, and 180 sec.

TABLE 6 Initial and final temperatures of test group, with carboncylinders INITIAL MAXIMUM FINAL TIME INTERVAL TEMPERATURE TEMPERATUREPIECE (s) (° C.) (° C.) 1 30 24.5 37.2 1 50 36.1 45.7 1 180 43.2 45.7 230 24.5 37.1 2 50 36.1 49.6 2 180 46.3 55.2 3 30 24.8 37.2 3 50 36.849.1 3 80 47.1 65.4 3 180 63.9 65.4 4 30 24.1 37.1 4 50 34.8 48.6 4 8047.7 73.4 4 100 73.2 75.0 4 180 68.1 75.0

As is seen in FIG. 5, the piece injected with the trilaurin-basedmixture reached its phase-change temperature quickly, and maintainedthis temperature throughout the experiment. The pieces injected withother phase-change materials, while taking somewhat longer to reachtheir respective phase-change temperatures, also maintained theirtemperatures at their respective phase-change temperatures throughoutthe experiment.

The following points may be observed from the experimental resultsillustrated by the graphs of FIGS. 3-5:

(a) Injection of a phase-change material into tissue can inhibit thetissue from being heated above a given temperature for a significantperiod of time. During this time, the phase-change material is absorbingheat energy as the latent heat of fusion of the phase change.

(b) Inserting carbon cylinders into tissue shortens the length of timerequired to heat the tissue to a given temperature, ceteris paribus,provided that the carbon cylinders have a diameter that is greater thana minimum diameter, e.g. 0.9 mm. It is noted that other materials thatare good energy absorbers, such as graphite and metals, may be used toshorten the length of time required to heat the tissue to a giventemperature.

Therefore, for some applications of the invention, as describedhereinabove, a phase-change material is inserted into a subject's tissueto facilitate the heating of the tissue to a given temperature and toinhibit the tissue from being heated above the given temperature. Forsome applications, an energy absorbing element 36 is inserted into asubject's tissue to facilitate the heating of the tissue, for example,by drawing energy from a heating device to the tissue, as describedhereinabove. Typically, energy absorbers that are biocompatible and thatdo not show artifacts in during imaging (e.g., X ray or MRI imaging) ofthe tissue, such as carbon or graphite cylinders, are inserted into thetissue. For some applications, carbon cylinders, each of the cylindershaving a diameter that is at least 0.9 mm, are inserted into the tissue.For some applications, an implantable, biocompatible metal, such asnitinol, stainless steel, cobalt and/or chromium, is used as an energyabsorbing element.

For some applications, energy is transmitted toward clusters ofphase-change molecules that are coupled to molecules (such as glucosemolecules), which, in turn, are coupled to cancer cells. In response tothe energy striking the clusters of phase-change molecules, thetemperature of the region in which the phase-change molecules aredisposed rises, but does not rise above the phase-change temperature ofthe phase-change molecules. This is because, at the phase-changetemperature, the heat that is transmitted toward the region is absorbedby the phase-change molecules as latent heat. The heating of thephase-change molecules typically heats the cancer cells, thereby killingthe cancer cells.

Reference is now made to FIG. 6, which is a schematic illustration of animplantable element 60 implanted within a portion of a subject's body,for example, a blood vessel 70 of the subject. The element includes ashape-memory material having a transformation temperature. Theimplantable element performs a first therapeutic function with respectto the blood vessel when the shape-memory material is in a first shape.An energy applicator 72 changes the shape-memory material from the firstshape to a second shape, by raising a temperature of the shape-memorymaterial to the transformation temperature. The second shape ismaintained even after energy applicator 72 no longer applies energy toimplantable element 60, and the temperature of implantable element 70returns to body temperature. When the shape-memory material is in thesecond shape, the implantable element performs a second therapeuticfunction with respect to the portion, the second therapeutic functionbeing qualitatively different from the first therapeutic function.

Typically, energy applicator 72 is an energy applicator as is known inthe art, for example, an RF generator, an ultrasound transducer, and/ora magnetic field generator. Further typically, element 60 contains ashape-memory material as is known in the art, for example, nitinol,copper-zinc-aluminum-nickel, and/or copper-aluminum-nickel.

Reference is now made to FIGS. 7A-B, which are schematic illustrationsof implantable element 60 in respective first and second configurations,in accordance with some applications of the present invention. For someapplications, implantable element 60 is a stent (as shown), which, in afirst configuration thereof, supports a narrowed blood vessel 70, inorder to open, and/or widen the blood vessel, as shown in FIG. 7A.Implantable element 60 is typically maintained in its firstconfiguration for a prolonged period (e.g., weeks or months, or adifferent period of time), until a desired effect of the stent has beenattained. Subsequently, energy applicator 72 raises the temperature ofthe stent to the transformation temperature of the shape change materialof the stent, and the shape of the stent changes to the shape of aventuri tube, as shown in FIG. 7B, i.e., a central portion of the stentnarrows.

For some applications, when the stent is in the second configuration, itcauses a controlled narrowing of blood vessel 70, region 73 of the bloodvessel wall collapsing to the outer wall of the stent. As a result ofthe narrowing of the blood vessel, blood flow (indicated by arrow 78)upstream of region 73 is impeded. In response to sensing impeded bloodflow, the body generates a new blood vessel 80 (not to scale), whichcircumvents the constriction of region 73. When the new blood vessel hasgenerated, the blood flows through the new blood vessel, in thedirection of arrow 82. This general physiological response of the bodyto an implanted venturi stent is described in PCT Publication WO03/028522 to Ben Muvhar, which is incorporated herein by reference.

For some applications of the present invention, a stent that contains ashape-memory material is implanted in an artery of a subject's brain,for example, a cerebral artery of the subject. In a first configurationthereof, the stent supports the artery in order to open, and/or widenthe artery. Subsequently, the temperature of the stent is raised to thetransformation temperature of the shape-memory material of the stent,causing the stent to expand. The expanded stent is used to facilitatedrug delivery across the subject's blood brain barrier, by increasingthe intercellular gaps of the blood brain barrier.

In a further application of the present invention, a stent that containsa shape-memory material is implanted in a subject's esophagus, in avicinity of an esophageal tumor. In a first configuration thereof, thestent supports the esophagus in order to open the esophagus in thevicinity of the tumor. Typically, the stent is configured to have adegree of flexibility that is sufficient to facilitate peristalsisthrough the esophagus, while the stent is disposed in the esophagus inthe first configuration thereof. Subsequently, the temperature of thestent is raised to the transformation temperature of the shape-memorymaterial of the stent, causing the stent to expand. Typically, the stentis expanded by a healthcare professional, in response to the tumorgrowing to a size such that it interferes with the ingestion of food bythe subject. The expanded stent pushes back the tumor, thereby wideningthe esophagus.

The scope of the present invention includes a shape-memory material thatis implanted in a subject's bone, the bone requiring elongation, forexample, subsequent to surgery on the bone. The shape-memory material issurgically coupled to the bone. Subsequently (for example, a day, a weekor a month after the implantation), the temperature of the shape-memorymaterial is raised, causing the shape-memory material to expand, and,consequently, causing the bone to lengthen. The shape-memory material isfurther expanded by repeatedly heating the shape-memory material (forexample, once every day, every week or every month, or as required),during the period of the bone elongation.

Reference is now made to FIGS. 8A-B, which are schematic illustrationsof a portion 90 of a drug pump, in accordance with some applications ofthe present invention. Portion 90 includes a drug chamber 92, ashape-memory material 94, and a separator 96 (e.g., a piston thatseparates the shape-memory material and the drug chamber). For someapplications, in order to release a given quantity of a drug 98 fromchamber 92, the shape-memory material is heated to its transformationtemperature, for a given time period. Upon heating the shape-memorymaterial to the transformation temperature (e.g., a temperature of 40-60C), the shape-memory material expands, as it undergoes a shape change,and releases the given quantity of the drug by advancing separator 96through a given distance, as shown in FIG. 8B.

For some applications, the heating of the shape-memory material isterminated before the shape-memory material has fully undergone itsshape-change. In a subsequent interaction, in order to dispense more ofthe drug, the shape-memory material is again heated to itstransformation temperature, thereby causing the shape-memory material tofurther expand, as it continues to undergo the shape change, thusreleasing more of the drug.

Typically, energy is applied to shape-memory material 94 by irradiatingthe shape-memory material, for example, using an RF generator, anultrasound transducer, and/or a magnetic field generator. Furthertypically, shape-memory material 94 is a shape-memory material that isknown in the art, for example, nitinol, copper-zinc-aluminum-nickel,and/or copper-aluminum-nickel. For some applications, the shape-memorymaterial expands by 5 percent to 25 percent, e.g. 8 percent to 12percent, in each interaction in which the shape-memory material isheated.

For some applications, portion 90 comprises a portion of an implantabledrug pump, the drug pump being as known in the art. For someapplications, portion 90 is used to administer insulin to a diabeticsubject. Alternatively or additionally, the portion is used toadminister a chemotherapy agent to a subject suffering from cancer.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

The invention claimed is:
 1. Apparatus for killing cancer cells of abody of a subject, the subject's body having cancer cells and healthycells, the apparatus comprising: a plurality of first moleculesconfigured to be coupled to the cancer cells to a greater extent than tothe healthy cells, in response to being administered to the subject; aplurality of molecules of a phase-change material, each of the firstmolecules being coupled to at least some of the phase-change materialmolecules, the phase-change material molecules being configured, uponbeing heated to a characteristic phase-change temperature of thephase-change material, to undergo a phase change selected from the groupconsisting of: wax to liquid, solid to liquid, solid to gel, and gel toliquid; and an energy transmission unit, configured to: kill cancercells coupled to the first molecules by heating the cancer cells to thephase-change temperature of the phase-change material, by transmittingenergy toward at least a portion of the subject's body, and avoidheating the phase-change material molecules above the phase-changetemperature of the phase-change material, by discontinuing thetransmission of energy after a given time period, the phase-changematerial molecules being configured to prevent a region of the subject'sbody in which the phase-change material molecules are disposed frombeing heated above the phase-change temperature, by the phase-changematerial molecules absorbing latent heat of fusion.
 2. The apparatusaccording to claim 1, wherein the energy transmission unit is configuredto rupture membranes of the cancer cells by heating the cancer cells. 3.The apparatus according to claim 1, wherein the energy transmission unitis configured to transmit energy at a resonance frequency of thephase-change material molecules.
 4. The apparatus according to claim 1,wherein the phase-change material molecules comprise paraffin molecules.5. The apparatus according to claim 1, wherein the phase-change materialmolecules comprise molecules of an organic phase-change material.
 6. Theapparatus according to claim 1, wherein the first molecules compriseglucose molecules.
 7. The apparatus according to claim 1, wherein thephase-change temperature of the phase-change material is between 60 and80 C.
 8. The apparatus according to claim 1, wherein the phase-changetemperature of the phase-change material is between 45 and 60 C.
 9. Amethod, for killing cancer cells of a body of a subject, the subject'sbody having the cancer cells and healthy cells, the method comprising:administering to the subject a plurality of first molecules, each of thefirst molecules having a plurality of molecules of a phase-changematerial coupled thereto, the first molecules being configured to becoupled to the cancer cells to a greater extent than to the healthycells, and the phase-change material molecules being configured, uponbeing heated to a characteristic phase-change temperature of thephase-change material, to undergo a phase change selected from the groupconsisting of: wax to liquid, solid to liquid, solid to gel, and gel toliquid; killing the cancer cells by heating the cancer cells to thephase-change temperature of the phase-change material, by transmittingenergy toward at least a portion of the subject's body; and avoidingheating the phase-change material molecules above the phase-changetemperature of the phase-change material, by discontinuing thetransmission of energy after a given time period, the phase-changematerial molecules preventing a region of the subject's body in whichthe phase-change material molecules are disposed from being heated abovethe phase-change temperature, by the phase-change material moleculesabsorbing latent heat of fusion.
 10. The method according to claim 9,wherein heating the cancer cells comprises rupturing membranes of thecancer cells.
 11. The method according to claim 9, wherein transmittingenergy toward the portion of the subject's body comprises irradiatingmultiple sites to which the cancer cells may have metastasized.
 12. Themethod according to claim 9, wherein transmitting energy toward theportion of the subject's body comprises transmitting energy at aresonance frequency of the phase-change material molecules.
 13. Themethod according to claim 9, wherein transmitting energy toward theportion of the subject's body comprises heating the portion of thesubject's body to a temperature of between 45 C and 60 C.
 14. The methodaccording to claim 9, wherein transmitting energy toward the portion ofthe subject's body comprises heating the portion of the subject's bodyto a temperature of between 60 C and 80 C.
 15. The method according toclaim 9, further comprising imaging the subject while transmittingenergy toward the portion of the subject's body.
 16. The methodaccording to claim 15, wherein imaging the subject comprises imaging thecancer cells using a heat-sensitive imaging protocol.